Furan-3-boronic acid → N-[1-(3-chloro-5-furan-3-yl-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide

HRID 878462Notes

Reaction equation

HRID 878462 reaction equation
[O:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.Br[C:10]1[CH:11]=[C:12]([Cl:31])[C:13]([C:16]2([CH2:19][NH:20][C:21](=[O:30])[C:22]3[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=3[F:29])[CH2:18][CH2:17]2)=[N:14][CH:15]=1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:31][C:12]1[C:13]([C:16]2([CH2:19][NH:20][C:21](=[O:30])[C:22]3[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=3[F:29])[CH2:18][CH2:17]2)=[N:14][CH:15]=[C:10]([C:3]2[CH:4]=[CH:5][O:1][CH:2]=2)[CH:11]=1

Participants

7

Reactant 2

HCID 2734358Furan-3-boronic acidHCID 89544494N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide

Product 1

HCID 71556053N-[1-(3-chloro-5-furan-3-yl-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamideYield 15.8%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent3×HCID 10340Sodium CarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 3-furylboronic acid (80 μmol) in toluene (0.3 ml) was added successively a solution of N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluorobenzamide (40 μmol) (from step 4) in toluene (0.5 ml), aqueous sodium carbonate 2M (0.06 ml), water (0.4 ml) and a solution of tetrakis(triphenylphosphine)palladium (4 μmol) in toluene (0.2 ml). The reaction mixture was stirred at 90° C. for 16 hours under an atmosphere of Argon. The reaction mixture was evaporated. The crude mixture was extracted 3 times with ethyl acetate and water. The organic phases were combined and evaporated. The crude product was dissolved in N,N-dimethylformamide (1ml) and purified by HPLC to give 2.45 mg N-[1-(3-chloro-5-furan-3-yl-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide.

Workup

  1. customThe reaction mixture was evaporated
  2. extractionThe crude mixture was extracted 3 times with ethyl acetate and water
  3. customevaporated
  4. dissolutionThe crude product was dissolved in N,N-dimethylformamide (1ml)
  5. custompurified by HPLC

Sources & evidence

ORD record
ord-796eb07929ac4ee584a96669794e8892
Source dataset
uspto-grants-2015_03
Patent number
US08987465B2

Reaction notes

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